1. Field of the Invention
The present invention relates to novel 5-fluorouracil derivatives, which are useful as carcinostatic substances.
2. Discussion of Related Art
5-Fluorouracil is known as a antimetabolite having a broad-spectrum antitumor activity and used in clinical therapy. However, it is highly toxic when orally administered and particularly accompanied with side effects such as disorders in the gastrointestinal.
To solve such drawbacks of 5-fluorouracil, many derivatives of 5-fluorouracil have been proposed. One of the early developed derivatives is 1-(2-tetrahydrofuryl)-5-fluorouracil. Although this compound is less toxic, its carcinostatic activity is weak so that it is not a satisfactory carcinostatic substance (cf. "Gan to Kagakuryouhou" (Cancer and Chemotherapy), 8, No. 11, 1811 (1981)).
To maintain the strong activity on one hand and to decrease the toxicity of 5-fluorouracil on the other hand, studies of the derivatives of 5-fluorouracil have been made. As a result, for example, 1-hexylcarbamoyl-5-fluorouracil was developed. This derivative is more suitable than the previous derivatives for oral administration, since it has stronger carcinostatic activity and lower toxicity against the gastrointestinal. However, since the metabolites produced from 1-hexylcarbamoyl-5-fluorouracil by the oxidation of the hexyl group in a liver causes autonomic imbalances such as frequency of feces, heat sensation and pollakiuria which are not found in the use of other 5-fluorouracil derivatives, as a practical matter, this derivative should be used together with a tranquilizer (cf. Pharmacia, 16, No. 6, 524-527 (1980)).